Effectiveness of EV-A71 vaccination in prevention of paediatric hand, foot, and mouth disease associated with EV-A71 virus infection requiring hospitalisation in Henan, China, 2017–18: a test-negative case-control study. (October 2019)

• Record Type: Journal Article
• Authors: Li, Yu; Zhou, Yonghong; Cheng, Yibing; Wu, Peng; Zhou, Chongchen; Cui, Peng; Song, Chunlan; Liang, Lu; Wang, Fang; Qiu, Qi; Guo, Chun; Zeng, Mengyao; Long, Lu; Cowling, Benjamin J; Yu, Hongjie
• Is Part Of: Lancet. Volume 3:Number 10(2019)
• Page Start: 697
• Page End: 704
• Publication Date: 2019-10
• Subjects: Pediatrics -- Periodicals; Children -- Health and hygiene -- Periodicals; Adolescent medicine -- Periodicals; Teenagers -- Health and hygiene -- Periodicals; 618.920005
• DOI: 10.1016/S2352-4642(19)30185-3
• Languages: English
• ISSNs: 2352-4642

Abstract

Summary: Background: Inactivated monovalent enterovirus A71 (EV-A71) vaccines are now available in China to reduce the substantial public health burden of hand, foot, and mouth disease. However, post-licensure monitoring of vaccine effectiveness is important. We did an observational test-negative study of EV-A71 vaccine effectiveness. Methods: Children with hand, foot, and mouth disease who were admitted to Henan Children's Hospital (Zhengzhou, China) within 7 days of illness onset were invited to participate in this test-negative case-control study. Participant vaccination history with EV-A71, including the number of doses received and the date of each dose of vaccination, was elicited from parents or legal guardians of participants with a standardised questionnaire. Children must have received two doses before hospitalisation to be counted as fully vaccinated. Patients who had received a single dose before hospitalisation were classified as partly vaccinated. Children who had received no EV-A71 vaccine before hospitalisation were classified as unvaccinated. Throat swabs and stool samples collected from patients were tested by RT-PCR to identify EV-A71 and other enteroviruses. The primary outcome of the study was paediatric hand, foot, and mouth disease associated with EV-A71 requiring hospitalisation. We estimated vaccine effectiveness with conditional logistic regression models adjusted for potential confounders. Findings: Between Feb 15, 2017, and Feb 15, 2018, we enrolled 1803 children aged 6–71 months with hand, foot, and mouth disease. 234 (13%) children tested positive for EV-A71, 1529 (85%) tested positive for other enteroviruses—528 (29%) were positive for Coxsackievirus (CV)-A6 and 342 (19%) were positive for CV-A16—and 29 (2%) tested negative for all enteroviruses. 11 (1%) children with neither throat swab nor stool testing results were excluded from further analyses. Overall vaccine effectiveness was estimated to be 85·4% (95% CI 53·2 to 95·4) for fully vaccinated children and 63·1% (13·1 to 84·3) for partly vaccinated children. The vaccine effectiveness for full vaccination was estimated to be 91·1% (35·1 to 98·8) among non-severe cases compared with 73·3% (−32·6 to 94·6) in severe cases. The vaccine effectiveness for partial vaccination was 77·9% (4·3 to 94·9) in children aged 24–71 months and 40·8% (−71·1 to 79·5) in children aged 6–23 months. We found no significant association between full or partial vaccination and CV-A6 or CV-A16-related hand, foot, and mouth disease. Interpretation: EV-A71 vaccination was effective in preventing non-severe hand, foot, and mouth disease associated with EV-A71 virus infection in children aged 6–71 months, and we found evidence that one dose of vaccination provided partial protection for children aged 24–71 months. Introduction of multivalent vaccines could further reduce the burden of hand, foot, and mouth disease. Funding: The National Science Fund for Distinguished Young Scholars.